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Islet NO-Synthases, extracellular NO and glucose-stimulated insulin secretion: Possible impact of neuronal NO-Synthase on the pentose phosphate pathway
The impact of islet neuronal nitric oxide synthase (nNOS) on glucose-stimulated insulin secretion (GSIS) is less understood. We investigated this issue by performing simultaneous measurements of the activity of nNOS versus inducible NOS (iNOS) in GSIS using isolated murine islets. Additionally, the significance of extracellular NO on GSIS was studied. Islets incubated at basal glucose showed modest nNOS but no iNOS activity. Glucose-induced concentration-response studies revealed an increase in both NOS activities in relation to secreted insulin. Culturing at high glucose increased both nNOS and iNOS activities inducing a marked decrease in GSIS in a following short-term incubation at high glucose. Culturing at half-maximal glucose showed strong iNOS expression revealed by fluorescence microscopy also in human islets. Experiments with nNOS-inhibitors revealed that GSIS was inversely related to nNOS activity, the effect of iNOS activity being negligible. The increased GSIS after blockade of nNOS was reversed by the intracellular NO-donor hydroxylamine. The enhancing effect on GSIS by nNOS inhibition was independent of membrane depolarization and most likely exerted in the pentose phosphate pathway (PPP). GSIS was markedly reduced, 50%, by glucose-6-phosphate dehydrogenase (G-6-PD) inhibition both in the absence and presence of nNOS inhibition. NO gas stimulated GSIS at low and inhibited at high NO concentrations. The stimulatory action was dependent on membrane thiol groups. In comparison, carbon monoxide (CO) exclusively potentiated GSIS. CO rather than NO stimulated islet cyclic GMP during GSIS. It is suggested that increased nNOS activity restrains GSIS, and that the alternative pathway along the PPP initially might involve as much as 50% of total GSIS. In the PPP, the acute insulin response is downregulated by a negative feedback effect executed by a marked upregulation of nNOS activity elicited from secreted insulin exciting insulin receptors at exocytotic sites of an nNOS-associated population of secretory granules.
Utility of complexity analysis in electroencephalography and electromyography for automated classification of sleep-wake states in mice
Structural design and safety performance of a novel high-strength steel lightweight guardrail
Highway guardrails are critical safety infrastructure along roadways, designed to redirect vehicles back into their lanes and facilitate a gradual deceleration to a complete stop. Traditional highway steel guardrails exhibit significant limitations, including inadequate energy absorption, susceptibility to corrosion, and an increased risk of vehicles leaving the roadway during severe collisions. Furthermore, the production and transportation of these guardrails contribute to substantial carbon emissions and environmental pollution. This study presents an optimization of the cross-sectional shape of the conventional corrugated beam guardrail, proposing a lightweight structure that incorporates high yield strength steel plate HR700F to enhance energy absorption capacity. The safety performance of the proposed guardrail is rigorously assessed through finite element numerical simulations and full-scale collision tests with real vehicles. Key performance indicators—such as the maximum dynamic lateral deflection of the guardrail, occupant impact velocity, and acceleration—are utilized to evaluate the energy absorption and protective efficacy of the structure. Results indicate that the optimized guardrail not only meets SB-level safety standards but also demonstrates superior anti-collision performance and effective energy absorption and buffering characteristics. The proposed design achieves a reduction in beam plate thickness by 1.3 mm, resulting in a lightweight structure with a weight reduction of up to 44%, thereby supporting the advancement of low-carbon, environmentally sustainable transportation solutions.
Impact of frequent ARID1A mutations on protein stability provides insights into cancer pathogenesis
Low regulatory T-cells frequency is associated with graft rejection after small bowel transplantation: Clinical and experimental evidence
Background Intestinal transplantation (ITx) represents the only curative option for patients with irreversible intestinal failure. Nevertheless, its rejection rate surpasses that of other solid organ transplants due to the heightened immunological load of the gut. Regulatory T-cells (Tregs) are key players in the induction and maintenance of peripheral tolerance, suggesting their potential involvement in modulating host vs. graft responses after ITx. Thus, we investigated the association of Tregs with allograft outcomes in pediatric patients and in an experimental model of small bowel transplantation. Methods Treg frequency in human samples was analyzed by Flow cytometry (CD4+CD25highCD127-, blood samples) and immunohistochemistry (FoxP3, graft samples). Experimental allogenic-heterotopic small bowel transplantation was performed in rats and animals divided into 3 groups: non-immunosuppressant treatment, rapamycin (2 mg/kg), and tacrolimus (0.6 mg/kg) treatment. Acute cellular rejection (ACR) was diagnosed based on clinical and histological findings, graft gene expression of pro- and anti-inflammatory mediators assessed by RT-qPCR, serum IL-6 and IL-10 levels by Luminex, and Treg frequency analyzed by flow cytometry (CD4+CD25highFoxP3+). Results Blood samples from patients undergoing ACR exhibited a significant reduction in the Treg number compared to those with normo-functional grafts. Similarly, a diminished number of FoxP3+ cells was observed in mucosa samples with ACR. In the experimental model, rapamycin-treated animals displayed clinical and histological findings resembling those not receiving immunosuppression treatment. Notably, ACR correlated with a high CD8/CD4 ratio, loss of T-cell chimerism, mRNA upregulation of pro-inflammatory genes and diminished graft Treg frequency. In contrast, tacrolimus treatment prevented ACR and facilitate blood and graft Treg expansion. Remarkably, recipients who achieved Treg expansion within the graft remained free of ACR even after discontinuation of the immunosuppressant treatment and this phenomenon was associated with increased levels of serum IL-10. Conclusion Our clinical and experimental findings underscore the association between Treg frequency and graft rejection after ITx, advocating for strategies that promote their expansion within the gut mucosa to enhance long-term outcomes.
Influence of the COVID-19 pandemic on the prevalence of depression in U.S. adults: evidence from NHANES
Exploring real estate blockchain adoption: An empirical study based on an integrated task-technology fit and technology acceptance model
Although many organizations have adopted blockchain technology (BCT) for efficiency and automation and users’ adoption of BCT is becoming crucial for the companies, few studies have focused on the factors affecting the adoption of BCT in real estate sector. This study aims to assess the factors affecting the adoption of BCT in real estate by the lens of an extended Technology Acceptance Model (TAM) and Task-technology fit (TTF). This current study uses quantitative survey approach. Data were collected from 311 real sector buyers and sellers in China. Partial least square structural equation modeling (PLS-SEM) was used for data analysis. The study’s findings indicate that attitude, perceived usefulness (PU) and data privacy and security (DPS) exerts highest influence in the proposed theoretical model. In addition, the findings also confirmed the significant impact of perceived ease of use (PEOU) on attitude, and TTF impact on PU and PEOU in adoption of BCT. Furthermore, the moderating impact of perceived compatibility (PC) on the relationship between TTF and PEOU was also confirmed. The study has useful practical implications for the real estate buyers and sellers that adoption of BCT improves efficiency, reduce transaction cost incur due to intermediaries, and enhance security system. Furthermore, the study suggests that automation achieved through BCT will facilitate customized agreements and improve process of title transfer.
Decreased PD-L1 contributes to preeclampsia by suppressing GM-CSF via the JAK2/STAT5 signal pathway
AI-assisted radiologists vs. standard double reading for rib fracture detection on CT images: A real-world clinical study
To evaluate the diagnostic accuracy of artificial intelligence (AI) assisted radiologists and standard double-reading in real-world clinical settings for rib fractures (RFs) detection on CT images. This study included 243 consecutive chest trauma patients (mean age, 58.1 years; female, 166) with rib CT scans. All CT scans were interpreted by two radiologists. The CT images were re-evaluated by primary readers with AI assistance in a blinded manner. Reference standards were established by two musculoskeletal radiologists. The re-evaluation results were then compared with those from the initial double-reading. The primary analysis focused on demonstrate superiority of AI-assisted sensitivity and the noninferiority of specificity at patient level, compared to standard double-reading. Secondary endpoints were at the rib and lesion levels. Stand-alone AI performance was also assessed. The influence of patient characteristics, report time, and RF features on the performance of AI and radiologists was investigated. At patient level, AI-assisted radiologists significantly improved sensitivity by 25.0% (95% CI: 10.5, 39.5; P < 0.001 for superiority), compared to double-reading, from 69.2% to 94.2%. And, the specificity of AI-assisted diagnosis (100%) was noninferior to double-reading (98.2%) with a difference of 1.8% (95% CI: -3.8, 7.4; P = 0.999 for noninferiority). The diagnostic accuracy of both radiologists and AI was influenced by patient gender, rib number, fracture location, and fracture type. Radiologist performance was affected by report time, whereas AI’s diagnostic accuracy was influenced by patient age and the side of the rib involved. AI-assisted additional-reader workflow might be a feasible strategy to instead of traditional double-reading, potentially offering higher sensitivity and specificity compared to standard double-reading in real-word clinical practice.
Multiomic machine learning on lactylation for molecular typing and prognosis of lung adenocarcinoma
Efficacy of different routes of triamcinolone acetonide administration on macular edema: A systematic review and network meta-analysis
There is different administration routes of triamcinolone acetonide (TA) administration for macular edema, but the efficacy ranking remains unclear. The purpose of this study is to assess the efficacy of different administration routes of TA employed in macular edema. PubMed, Medline, Embase, and Cochrane Central Register of Controlled Trials were systematically searched for published articles comparing macular edema in patients with triamcinolone acetonide in different administration. The sparse network was evaluated using a random-effects model and consistency model within the Bayesian framework, utilizing the multinma package in R. The evidence was assessed based on the Grading of Recommendations. Assessment, Development, and Evaluation (GRADE) criteria. A total of 1138 citations were identified by our search, of which 20 RCTs enrolled 892 eyes. The network showed that intravitreal triamcinolone acetonide (IVTA) was associated with a statistically significant better best corrected visual acuity (BCVA) at the 12th week compared to placebo (MD: − 0.15, 95% CI: − 0.30 to − 0.01, P < 0.05), which was moderate-quality evidence. IVTA and suprachoroidal triamcinolone acetonide (SCTA) were both associated with a statistically significant reduction in central macular thickness (CMT) at the 12th week, which was moderate evidence. The probabilities of rankings and SUCRA demonstrated that sub-Tenon’s infusion of triamcinolone acetonide (STiTA) might be the worst. SCTA and IVTA were proven to be the best administration routes for improving BCVA and reducing CMT. In addition, STiTA was less advisable than other administration routes of triamcinolone acetonide according to the rankings and SUCRA.
Primary tumor resection might improve outcomes in metastatic thoracic esophageal cancer
Examining hurricane–related social media topics longitudinally and at scale: A transformer-based approach
Instead of turning to emergency phone systems, social media platforms, such as Twitter, have emerged as alternative and sometimes preferred venues for members of the public in the US to communicate during hurricanes and other natural disasters. However, relevant posts are likely to be missed by responders given the volume of content on platforms. Previous work successfully identified relevant posts through machine-learned methods, but depended on human annotators. Our study indicates that a GPU-accelerated version of BERTopic, a transformer-based topic model, can be used without human training to successfully discern topics during multiple hurricanes. We use 1.7 million tweets from four US hurricanes over seven years and categorize identified topics as temporal constructs. Some of the more prominent topics related to disaster relief, user concerns, and weather conditions. Disaster managers can use our model, data, and constructs to be aware of the types of themes social media users are producing and consuming during hurricanes.
Connecting electronic health records to a biomedical knowledge graph to link clinical phenotypes and molecular endotypes in atopic dermatitis
A spatial interpolation method based on 3D-CNN for soil petroleum hydrocarbon pollution
Petroleum hydrocarbon pollution causes significant damage to soil, so accurate prediction and early intervention are crucial for sustainable soil management. However, traditional soil analysis methods often rely on statistical methods, which means they always rely on specific assumptions and are sensitive to outliers. Existing machine learning based methods convert features containing spatial information into one-dimensional vectors, resulting in the loss of some spatial features of the data. This study explores the application of Three-Dimensional Convolutional Neural Networks (3DCNN) in spatial interpolation to evaluate soil pollution. By introducing Channel Attention Mechanism (CAM), the model assigns different weights to auxiliary variables, improving the prediction accuracy of soil hydrocarbon content. We collected soil pollution data and validated the spatial distribution map generated using this method based on the drilling dataset. The results indicate that compared with traditional Kriging3D methods (R2 = 0.318) and other machine learning methods such as support vector regression (R2 = 0.582), the proposed 3DCNN based method can achieve better accuracy (R2 = 0.954). This approach provides a sustainable tool for soil pollution management, supports decision-makers in developing effective remediation strategies, and promotes the sustainable development of spatial interpolation techniques in environmental science.
Advancing neutron imaging techniques to highest resolution with fluorescent nuclear track detectors
Analysis of seroprevalence and risk factors for syphilis and HIV among female sex workers and transgender individuals in different cities of Sindh, Pakistan
Introduction Co-infections of syphilis and HIV have been found to exacerbate the impact on sexual and reproductive health, especially among key population groups such as Female Sex Workers (FSWs) and Transgender Individuals (TGs). The data on the prevalence and determinants of syphilis and HIV in Pakistan, particularly in Sindh province, is limited. This prospective cross-sectional study aimed to determine the seroprevalence and risk factors for HIV and syphilis infections among FSWs and TGs in different cities of Sindh, Pakistan. Methods A total of 1120 participants (531 FSWs and 589 TGs) were recruited from Karachi, Sukkur, Hyderabad, and Larkana. Community-based serological testing for HIV and syphilis was performed using Abbot Bioline HIV/syphilis Duo test kits, and sociodemographic and risk factor data were collected through questionnaires. Chi-square and logic regression were applied to determine variables associated significantly with syphilis in TGs and FSWs. Results TGs exhibited higher rates of syphilis (16.29%) and syphilis-HIV (6.79%) as compared to FSWs (syphilis: 15.63%; syphilis-HIV: 0.75%). Inconsistent condom use was more common among FSWs (75.32%), and over half reported STI symptoms. Regression analysis showed that for TGs, having five years (adjusted OR: 0.52, p = 0.04) and graduate-level education (adjusted OR: 0.40, p = 0.04) was associated with a lower risk of syphilis, while an income between 30,000 and 50,000 Pakistani rupees (OR: 1.93, p = 0.028) and more than three years in profession (adjusted OR: 2.20, p = 0.04) was associated with a higher risk. For FSWs, five (OR: 0.34, p = 0.03) and ten (OR: 0.02, p = 0.02) years of education were associated with a lower risk of syphilis, whereas an income between 30,000 and 50,000 PKR (OR: 3.05, p < 0.01) and self-reported HIV-negative status (OR: 3.08, p = 0.01) were associated with a higher risk of syphilis mono-infection. Conclusion In conclusion, the results of the study show higher rates of syphilis and HIV co-infection among TG compared to FSW from Sind. The study findings provide valuable insights for national health agencies and policymakers to devise data-driven strategies for preventing and controlling syphilis and HIV infections among FSW and TG populations in Sind.
In situ forming gels as subcutaneous delivery systems of curcumin and piperine
Environmental judicature and firm productivity: Evidence from a quasi-natural experiment
The impact of environmental governance on firm productivity has been widely discussed, but few studies have examined the function of environmental judicature. Using the establishment of environmental courts as a quasi-natural experiment, this paper examines the relationship between environmental judicature and firm productivity. Our findings show that environmental courts will reduce firm productivity in the short term, chiefly owing to the increased environmental violation costs, environmental reputation costs and environmental compliance costs. The conclusion remains robust after mitigation of heterogeneous treatment effects, PSM-DID estimation, placebo tests and IV estimation. This negative effect is more pronounced for firms located in regions with high legal scores and low government intervention, for firms located in the eastern region, for firms with weak market power, and for firms with high pollution intensity. In addition, our further analysis suggests that environmental courts would improve the long-term firm productivity and regional green productivity, indicating that strengthening environmental judicature are conducive to firms’ sustainable growth and regions’ green transformation in the long run.